Analysis of cell death and repair pathway choice of DNA double-strand breaks caused by anti-cancer drug

• Project/Area Number: 24710061
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Kanazawa Medical University
• Principal Investigator: Sakasai Ryo 金沢医科大学, 医学部, 助教 (10549950)
• Research Collaborator: SHIBATA Atsushi 群馬大学, 先端科学研究指導者育成ユニット, 助教 (30707633)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: DNA二本鎖切断 / 非相同末端連結 / 相同組換え / カンプトテシン / ユビキチン

Outline of Final Research Achievements

DNA double-strand breaks (DSBs) are severe DNA damage that can be caused by anti-cancer drug to kill cancer cells. Camptothecin (CPT) causes DSB via DNA replication in growing cells. However, cellular responses to DNA replication-mediated DSB (RM-DSB) had not been revealed. In this study, we analyzed regulatory mechanisms of RM-DSB repair pathway and discovered that UbcH5c, a E2 ubiquitin-conjugating enzyme, is involved in NHEJ pathway of RM-DSB repair leading to chromosomal aberration.

Research Products

• [Journal Article] The distinctive cellular responses to DNA strand breaks caused by a DNA topoisomerase I poison in conjunction with DNA replication and RNA transcription (2015)
  • Author(s): Sakasai R, Iwabuchi K.
  • Journal Title: Genes & Genetic Systems Volume: 90 Issue: 4 Pages: 187-194
  • DOI: 10.1266/ggs.15-00023
  • NAID: 130005118395
  • ISSN: 1341-7568, 1880-5779
  • Peer Reviewed
• [Presentation] Ubiquitin-dependent activation of DNA-PKcs leads to chromosomal aberration in response to one-ended DNA double strand breaks (2015)
  • Author(s): Ryo Sakasai, Yumi Sunatani, Tadashi Matsui, Mitsumasa Hashimoto, Kuniyoshi Iwabuchi
  • Organizer: ICRR2015
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Ubiquitin-dependent activation of DNA-PKcs in response to DNA replication-mediated DNA double strand breaks (2014)
  • Author(s): Ryo Sakasai, Yumi Sunatani, Tadashi Matsui, Mitsumasa Hashimoto, Kuniyoshi Iwabuchi
  • Organizer: The 9th 3R Symposium
  • Place of Presentation: 御殿場高原ホテル時之栖（静岡県御殿場市）
  • Year and Date: 2014-11-17 – 2014-11-21
• [Presentation] ユビキチン化を介したDNA-PKcs活性化機構 (2014)
  • Author(s): 逆井良、松井理、砂谷優実、橋本光正、岩淵邦芳
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: かごしま県民交流センター（鹿児島県鹿児島市）
  • Year and Date: 2014-10-01 – 2014-10-03
• [Remarks] Iwabuchi Lab 金沢医科大学 生化学I
  • URL: http://kmu-bc1.jimdo.com
• [Remarks] Iwabuchi Lab-金沢医科大学 生化学I
  • URL: http://kmu-bc1.jimdo.com